Complex chromosomal rearrangements associated with congenital erythrophagocytotic histiocytosis

We describe a patient with a congenital malignant blood disorder and a constitutional de novo chromosomal rearrangement that includes four breakpoints. By conventional cytogenetic analysis an obviously reciprocal balanced translocation with the breakpoints 1p36 and 5q11.2 was diagnosed. Due to a suspicious dark band in the breakpoint area of 1p a more detailed analysis of the breakpoints was performed using microdissection and reverse chromosome painting. This revealed a small inversion at 1p36 that must have occurred prior to the reciprocal translocation. The three breakpoints in chromosome 1 (1p36.11, 1p36.21 and 1p36.31) are within or close by regions known to contain tumor suppressor genes. The chromosomal rearrangement might have resulted either in a submicroscopic deletion, in loss of heterozygosity of one or more imprinted genes, or in gene position effects as possible explanations for the clinical course of our patient.